Triethylamine → Methyl 4-[(1S)-1-({5-chloro-2-[(2-chlorophenoxy)methyl]benzoyl}amino)ethyl]benzoate

HRID 660199Notes

Reaction equation

HRID 660199 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[NH2:21][C@H:22]([C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1)[CH3:23].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])=[C:6]([CH:10]=1)[C:7]([NH:21][C@H:22]([C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1)[CH3:23])=[O:9]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57462942(S)-Methyl 4-(1-aminoethyl)benzoate hydrochlorideHCID 688644305-Chloro-2-[(2-chlorophenoxy)methyl]benzoic acid

Product 1

HCID 68861972Methyl 4-[(1S)-1-({5-chloro-2-[(2-chlorophenoxy)methyl]benzoyl}amino)ethyl]benzoateYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-chloro-2-[(2-chlorophenoxy)methyl]benzoic acid (step 2, 85 mg, 0.28 mmol), methyl 4-[(1S)-1-aminoethyl]benzoate hydrochloride (step 5, 73 mg, 0.34 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (107 mg, 0.56 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (76 mg, 0.56 mmol) and triethylamine (117 μL, 0.84 mmol) in dichloromethane (3 mL) was stirred at room temperature for 19 hours. Water (5 mL) was added and the organic phase was separated. The aqueous phase was extracted with ethyl acetate (10 mL×2) and the combined organic extracts were dried (sodium sulfate). After removal of solvent, the residue was purified by pTLC eluting with hexane/ethyl acetate (2/1) to afford 105 mg (82%) of the title compound:

Workup

  1. customthe organic phase was separated
  2. extractionThe aqueous phase was extracted with ethyl acetate (10 mL×2)
  3. dry with materialthe combined organic extracts were dried (sodium sulfate)
  4. customAfter removal of solvent
  5. customthe residue was purified by pTLC
  6. washeluting with hexane/ethyl acetate (2/1)

Sources & evidence

ORD record
ord-b23c7b99d0ae4b8297b3504e28059ca9
Source dataset
uspto-grants-2011_12
Patent number
US08084476B2

Reaction notes

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